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S. Kotha et al. / Bioorg. Med. Chem. Lett. 10 (2000) 1755±1757
Table 1.
S. no.
Sultine structure
Yield
83%
Diels±Alder product
Yield/conditions
1
2
66% benzene re¯ux 20 h
34%
57%
63% toluene re¯ux 40 h
3
64% toluene sealed tube/130 ꢀC 48 h
4
5
35%
60%
35% xylene 80 ꢀC 42 h
91% toluene sealed tube/130 ꢀC 72 h
6
20%
40% xylene 110 ꢀC 34 h
120 ꢀC) and found that no Diels±Alder product was
observed. Since the parent BCB undergoes thermal
cyclobutene ring opening at 200 ꢀC,11 BCB (8, RH)
and 5 was reacted in xylene in a sealed tube at 180±
200 ꢀC and found several products as indicated by TLC
analysis. At this juncture it occurred to us that a milder
method for the generation of o-xylylene such as 4 is
desirable in the present case. Moreover, generation of 4 in
the absence of dienophile is known to undergo dimeriza-
tion and/or polymerization to generate unwanted pro-
ducts. A perusal of literature indicated that generation
of o-xylylene such as 4 by thermal elimination of sulfur
dioxide from sultine, l,4-diliydro-2,3-benzoxathiin-3-
oxide 7 requires lower temperature than the other benzo-
fused cyclic precursors. Accordingly, to test our idea, the
parent sultine12 was prepared and reacted with 5 at ben-
zene re¯ux temperature gave the required product in
66% isolated yield.
peptides, our results may be of interest to medicinal and
bioorganic chemists working in these areas.
Acknowledgements
We thank DST for ®nancial support and RSIC-Mumbai
for recording the spectral data.
References and Notes
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3. Hruby, V. J. Biopolymers 1993, 33, 1073.
Having established the conditions for trapping o-xyly-
lene in the presence of 5, next we turned our attention to
expand this strategy to other related substrates. Various
tetralin-based AAA prepared in this regard are outlined
in Table 1. All these compounds are identi®ed by their
complementary spectral data.13
4. Bhandari, A.; Jones, D. G.; Schullek, J. R.; Vo, K.;
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In conclusion, we have shown that various o-xylylene
derivatives derived from sultines are trapped with 2-
acetamidoacrylate 5 in a Diels±Alder fashion to gen-
erate various tetralin-based constrained AAA deriva-
tives. It is worth mentioning that compounds of type 22
are inaccessible by the currently available methods due
to the presence of keto functionality. Moreover, the
starting keto precursors sensors for BB method is not a
trivial exercise. Since constrained AAA derivatives play
an important role in the design of biologically active
Kotha, Sambasivarao
